Dementia
Conditions
Keywords
Dementia, Mixed Dementia, Galantamine, Reminyl ER, Nimodipine
Brief summary
The purpose of this study is to evaluate the combination of galantamine with nimodipine in patients with mixed dementia on cognition and quality of life.
Detailed description
A double-blind (neither the patient nor the physician know the name of the study drug), 6-month, multicenter, placebo-controlled trial to evaluate the combination of galantamine with nimodipine in patients with mixed dementia on cognition and quality of life. The target dose of galantamine is 24 mg/day and nimodipine will be taken in fixed doses of 90 mg/day. Primary outcomes will be measured by a computerized battery of neuropsychological tests and Quality of Life (QoL) scores. Secondary outcomes will be measured by ADAS-cog, Clinical Global Impression (CGI) and Neuropsychiatric Inventory (NPI). Mixed dementia (Alzheimer's Disease (AD) associated with cerebrovascular disease) is one of the most common causes of dementia, which remain largely underdiagnosed. Little is known about specific treatments for this condition. Ischemic lesions by themselves seem to play an important role in cognitive impairment, even in the presence of AD pathology. Hypotheses: - Galantamine 16-24 mg/day in combination with nimodipine 90 mg/day is superior to galantamine monotherapy (16-24 mg/day) in improving or stabilizing cognition in patients with AD associated with cerebrovascular disease (mixed dementia), as measured by the CNTB at 6 months. - Galantamine 16-24 mg/day in combination with nimodipine 90 mg/day is superior to galantamine monotherapy (16-24 mg/day) on QoL measures in this population as measured by QoL - AD at 6 months. Group 1: galantamine oral 8mg/day for a month, 16mg/day for 4 weeks and after 24mg/day until end of study plus nimodipine oral 30mg tid during all study. Group 2: Group 1: galantamine oral 8mg/day for a month, 16mg/day for 4 weeks and after 24mg/day until end of study plus placebo oral 30mg tid during all study.
Interventions
DRUGGalantamine
Galantamine 8 mg/day for one month, followed by 4 weeks of galantamine 16 mg/day. If necessary and well tolerated, dosage of galantamine will be increased to 24 mg/day.
DRUGNimodipine
Nimodipine 30 mg 3 times a day (tid).
DRUGPlacebo
Matching placebo three times a day (tid).
Sponsors
Janssen-Cilag Farmaceutica Ltda.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients should fulfill DSM-IV criteria for dementia (APA, 1994) * Patients should fulfill criteria for AD with cerebrovascular disease according to NINDS-AIREN criteria (Román et al., 1993) * The severity of dementia should be mild to moderate, as defined by MMSE score between 10 and 26 (inclusive) * Patients (and their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
Exclusion criteria
* History of neurodegenerative disorders such as Parkinson's disease, Pick's disease or Huntington's chorea, Down's syndrome, Creutzfeldt-Jacob disease. Patients who have mild extrapyramidal signs, for which no treatment is required, are not excluded from the trial * History of liver or renal insufficiency * significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, psychiatric, or metabolic disturbances in the past 6 months * Patients who have previously received M1 agonists or cholinesterase inhibitors (tacrine, donepezil, metrifonate, rivastigmine) for treatment of Alzheimer's disease, no matter if approved or experimental can be included in this trial provided there was at least a washout period of 60 days prior to the screening assessments * History of drug or alcohol abuse within the last year or prior prolonged history * History of severe drug allergy or hypersensitivity * including recorded hypersensitivity to cholinesterase inhibitors, choline agonists or similar agents, or bromide * Subjects who have previously been enrolled in other galantamine trials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores, Based on the Caregiver's Opinion, at Baseline, Week 8, Week 24 | Baseline, Week 8, Week 24 | The Quality of Life assessment scale for patients with Alzheimer's disease (QoL-AD), according to the opinion of the caregiver is a 13-item scale with four possible scores for each question (score 1: poor and score 4: excellent). It evaluates the opinion of the caregiver about the patient's quality of life. Total score ranges from 13 to 52. Higher scores represent a better outcome. |
| Reaction Time for Word Recognition and Learning Test at Baseline, Week 8, and Week 24 | Baseline, Week 8, Week 24 | The reaction time for word recognition and learning test is a computerized attention test that evaluates the patient's reaction time. This test is similar to the Face Recognition test procedure using Words. The recognition procedure was repeated three times to evaluate a learning effect. The reaction time, assessed per patient, was averaged at each time point for each patient e.g., at baseline, Week 8 and Week 24. This test is part of the Computerized Neuropsychological Test Battery (CNTB). |
| The Quality of Life Assessment for Caregivers of Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | Baseline, Week 8, Week 24 | The Quality of Life assessment scale for caregivers of patients with Alzheimer's disease (QoL-AD) is a 13-item scale with four possible scores for each question (score 1: poor and score 4: excellent). It evaluates the caregivers own perceived quality of life. Total score ranges from 13 to 52. Higher scores represent a better outcome. |
| The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | Baseline, Week 8, Week 24 | The Quality of Life assessment scale for patients with Alzheimer's disease (QoL-AD) is a 13-item scale with four possible scores for each question (score 1: poor and score 4: excellent). Total score ranges from 13 to 52. Higher scores represent a better outcome. |
| Reaction Time for Simple Reaction Time Test at Baseline, Week 8, and Week 24 | Baseline, Week 8, Week 24 | The Simple Reaction Time is a computerized attention test that evaluates the patient's reaction time. The number one was presented in the center of the computer screen and the patient had to press this number in the response box as quickly as possible. The reaction time, assessed 100 times per patient, was averaged at each time point for each patient e.g., at baseline, Week 8 and Week 24. The patient's finger was put over button one before the test begun. This test is part of the Computerized Neuropsychological Test Battery (CNTB). |
| Reaction Time for Two-choice Reaction Time Test at Baseline, Week 8, and Week 24 | Baseline, Week 8, Week 24 | The Two-choice reaction time test is a computerized attention test in which the numbers one or five were presented in the center of the computer screen in a random order. The patient had to press the correspondent button in the response box as quickly as possible. The patient's right finger was put over the button five and the left finger over button one before the test begun. The reaction time, assessed 100 times per patient, was averaged at each time point for each patient e.g., at baseline, Week 8 and Week 24.This test is part of the Computerized Neuropsychological Test Battery (CNTB). |
| Reaction Time for Face Recognition Test at Baseline, Week 8, and Week 24 | Baseline, Week 8, Week 24 | The face recognition test is a computerized attention test in which ten unfamiliar faces were presented simultaneously on the computer screen for ten seconds to be remembered. After that, a single face was shown and the patient had to press the button one if he/she remembered or, otherwise, button five. It consisted of a random presentation of ten pre-exposed faces and ten new faces as distracters. The reaction time, assessed per patient, was averaged at each time point for each patient e.g., at baseline, Weeks 8 and 24. This test is part of the Computerized Neuropsychological Test Battery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Week 4, Week 8, Week 16, Week 24 | The Clinical Global Impression (CGI) is a scale to assess treatment response in patients with mental disorders. The Clinical Global Impression Improvement scale (CGI-I) requires the clinician to rate how much the patient's illness has improved or worsened relative to a baseline state. A patient's illness is compared to change over time and rated as: very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. |
| The Neuropsychiatric Inventory (NPI) at Baseline, Week 8, and Week 24 | Baseline, Week 8, Week 24 | The NPI evaluates 12 neuropsychiatric domains: delusions, hallucinations, dysphoria, anxiety, aggression, euphoria, dis-inhibition, irritability/lability, apathy, aberrant motor activity, eating disorders, and night-time behavior disturbances. For present domains, the severity and frequency of the behavior are determined. Frequency is rated 1 (rarely) to 4 (very often) and Severity is scored 1 (mild) to 3 (severe). The product scores vary from 1 (mild and rarely) to 12 (very often and severe). Total scores vary from 0 (no present domain) to 144 (all domains are present, are often and severe). |
| The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Baseline, Week 8, and Week 24 | Baseline, Week 8, Week 24 | The ADAS-Cog is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation and praxis using an 11-point Assessment Scale. It has a minimum score of 0 and a maximum severity score of 70, and a higher score indicates more impairment. |
Participant flow
Pre-assignment details
22 patients were enrolled in the study, but one (1) patient was excluded from the study because the patient has died before study medication use. Therefore, the study was formed by 21 patients that used at least 1 study medication dose and had at least 1 evaluation after started use (Intention to Treat (ITT) population).
Participants by arm
| Arm | Count |
|---|---|
| Galantamine + Nimodipine Galantamine 8 mg/day for one month + nimodipine 30 mg 3 times a day (tid), followed by 4 weeks of galantamine 16 mg/day + nimodipine 30 mg tid. If necessary and well tolerated, dosage of galantamine will be increased to 24 mg/day + nimodipine 30 mg tid. | 9 |
| Galantamine + Placebo Galantamine 8 mg/day and placebo three times a day (tid) for 4 weeks, followed by 4 weeks of galantamine 16 mg/day and placebo tid. If necessary and well tolerated, galantamine dosage may be increased to 24 mg/day, together with placebo tid. | 12 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Galantamine + Nimodipine | Galantamine + Placebo | Total |
|---|---|---|---|
| Age Continuous | 78.1 years STANDARD_DEVIATION 5.3 | 74.3 years STANDARD_DEVIATION 6.5 | 76.0 years STANDARD_DEVIATION 6.2 |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 15 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 9 | 10 / 12 |
| serious Total, serious adverse events | 1 / 9 | 1 / 12 |
Outcome results
Primary
Reaction Time for Face Recognition Test at Baseline, Week 8, and Week 24
The face recognition test is a computerized attention test in which ten unfamiliar faces were presented simultaneously on the computer screen for ten seconds to be remembered. After that, a single face was shown and the patient had to press the button one if he/she remembered or, otherwise, button five. It consisted of a random presentation of ten pre-exposed faces and ten new faces as distracters. The reaction time, assessed per patient, was averaged at each time point for each patient e.g., at baseline, Weeks 8 and 24. This test is part of the Computerized Neuropsychological Test Battery.
Time frame: Baseline, Week 8, Week 24
Population: Intent to Treat population, which consisted of all participants who used at least 1 study medication dose, had at least 1 evaluation after started use, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine + Nimodipine (Baseline) | Reaction Time for Face Recognition Test at Baseline, Week 8, and Week 24 | 3124.00 milliseconds | Standard Deviation 1461.46 |
| Galantamine + Placebo (Baseline) | Reaction Time for Face Recognition Test at Baseline, Week 8, and Week 24 | 2684.45 milliseconds | Standard Deviation 1315.44 |
| Galantamine + Nimodipine (Week 8) | Reaction Time for Face Recognition Test at Baseline, Week 8, and Week 24 | 2262.50 milliseconds | Standard Deviation 803.3 |
| Galantamine + Placebo (Week 8) | Reaction Time for Face Recognition Test at Baseline, Week 8, and Week 24 | 2734.25 milliseconds | Standard Deviation 1252.62 |
| Galantamine + Nimodipine (Week 24) | Reaction Time for Face Recognition Test at Baseline, Week 8, and Week 24 | 2357.80 milliseconds | Standard Deviation 1919.72 |
| Galantamine + Placebo (Week 24) | Reaction Time for Face Recognition Test at Baseline, Week 8, and Week 24 | 3099.38 milliseconds | Standard Deviation 1823.8 |
Primary
Reaction Time for Simple Reaction Time Test at Baseline, Week 8, and Week 24
The Simple Reaction Time is a computerized attention test that evaluates the patient's reaction time. The number one was presented in the center of the computer screen and the patient had to press this number in the response box as quickly as possible. The reaction time, assessed 100 times per patient, was averaged at each time point for each patient e.g., at baseline, Week 8 and Week 24. The patient's finger was put over button one before the test begun. This test is part of the Computerized Neuropsychological Test Battery (CNTB).
Time frame: Baseline, Week 8, Week 24
Population: Intent to Treat population, which consisted of all participants who used at least 1 study medication dose, had at least 1 evaluation after started use, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine + Nimodipine (Baseline) | Reaction Time for Simple Reaction Time Test at Baseline, Week 8, and Week 24 | 1024.06 milliseconds | Standard Deviation 1307.97 |
| Galantamine + Placebo (Baseline) | Reaction Time for Simple Reaction Time Test at Baseline, Week 8, and Week 24 | 729.18 milliseconds | Standard Deviation 394.88 |
| Galantamine + Nimodipine (Week 8) | Reaction Time for Simple Reaction Time Test at Baseline, Week 8, and Week 24 | 466.60 milliseconds | Standard Deviation 297.53 |
| Galantamine + Placebo (Week 8) | Reaction Time for Simple Reaction Time Test at Baseline, Week 8, and Week 24 | 671.33 milliseconds | Standard Deviation 298.38 |
| Galantamine + Nimodipine (Week 24) | Reaction Time for Simple Reaction Time Test at Baseline, Week 8, and Week 24 | 467.60 milliseconds | Standard Deviation 336.69 |
| Galantamine + Placebo (Week 24) | Reaction Time for Simple Reaction Time Test at Baseline, Week 8, and Week 24 | 584.44 milliseconds | Standard Deviation 320.37 |
Primary
Reaction Time for Two-choice Reaction Time Test at Baseline, Week 8, and Week 24
The Two-choice reaction time test is a computerized attention test in which the numbers one or five were presented in the center of the computer screen in a random order. The patient had to press the correspondent button in the response box as quickly as possible. The patient's right finger was put over the button five and the left finger over button one before the test begun. The reaction time, assessed 100 times per patient, was averaged at each time point for each patient e.g., at baseline, Week 8 and Week 24.This test is part of the Computerized Neuropsychological Test Battery (CNTB).
Time frame: Baseline, Week 8, Week 24
Population: Intent to Treat population, which consisted of all participants who used at least 1 study medication dose, had at least 1 evaluation after started use, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine + Nimodipine (Baseline) | Reaction Time for Two-choice Reaction Time Test at Baseline, Week 8, and Week 24 | 1919.72 milliseconds | Standard Deviation 1801.13 |
| Galantamine + Placebo (Baseline) | Reaction Time for Two-choice Reaction Time Test at Baseline, Week 8, and Week 24 | 1096.75 milliseconds | Standard Deviation 617.45 |
| Galantamine + Nimodipine (Week 8) | Reaction Time for Two-choice Reaction Time Test at Baseline, Week 8, and Week 24 | 852.70 milliseconds | Standard Deviation 480.79 |
| Galantamine + Placebo (Week 8) | Reaction Time for Two-choice Reaction Time Test at Baseline, Week 8, and Week 24 | 1187.78 milliseconds | Standard Deviation 637.6 |
| Galantamine + Nimodipine (Week 24) | Reaction Time for Two-choice Reaction Time Test at Baseline, Week 8, and Week 24 | 727.60 milliseconds | Standard Deviation 375.03 |
| Galantamine + Placebo (Week 24) | Reaction Time for Two-choice Reaction Time Test at Baseline, Week 8, and Week 24 | 1116.25 milliseconds | Standard Deviation 540.91 |
Primary
Reaction Time for Word Recognition and Learning Test at Baseline, Week 8, and Week 24
The reaction time for word recognition and learning test is a computerized attention test that evaluates the patient's reaction time. This test is similar to the Face Recognition test procedure using Words. The recognition procedure was repeated three times to evaluate a learning effect. The reaction time, assessed per patient, was averaged at each time point for each patient e.g., at baseline, Week 8 and Week 24. This test is part of the Computerized Neuropsychological Test Battery (CNTB).
Time frame: Baseline, Week 8, Week 24
Population: Intent to Treat population, which consisted of all participants who used at least 1 study medication dose, had at least 1 evaluation after started use, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine + Nimodipine (Baseline) | Reaction Time for Word Recognition and Learning Test at Baseline, Week 8, and Week 24 | 2022.17 milliseconds | Standard Deviation 672.08 |
| Galantamine + Placebo (Baseline) | Reaction Time for Word Recognition and Learning Test at Baseline, Week 8, and Week 24 | 2978.77 milliseconds | Standard Deviation 1867.62 |
| Galantamine + Nimodipine (Week 8) | Reaction Time for Word Recognition and Learning Test at Baseline, Week 8, and Week 24 | 1966.40 milliseconds | Standard Deviation 1252.1 |
| Galantamine + Placebo (Week 8) | Reaction Time for Word Recognition and Learning Test at Baseline, Week 8, and Week 24 | 2379.83 milliseconds | Standard Deviation 984.52 |
| Galantamine + Nimodipine (Week 24) | Reaction Time for Word Recognition and Learning Test at Baseline, Week 8, and Week 24 | 1722.00 milliseconds | Standard Deviation 1174.22 |
| Galantamine + Placebo (Week 24) | Reaction Time for Word Recognition and Learning Test at Baseline, Week 8, and Week 24 | 3038.81 milliseconds | Standard Deviation 1243.79 |
Primary
The Quality of Life Assessment for Caregivers of Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24
The Quality of Life assessment scale for caregivers of patients with Alzheimer's disease (QoL-AD) is a 13-item scale with four possible scores for each question (score 1: poor and score 4: excellent). It evaluates the caregivers own perceived quality of life. Total score ranges from 13 to 52. Higher scores represent a better outcome.
Time frame: Baseline, Week 8, Week 24
Population: Intent to Treat population, which consisted of all participants who used at least 1 study medication dose, had at least 1 evaluation after started use, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine + Nimodipine (Baseline) | The Quality of Life Assessment for Caregivers of Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | 34.00 scores on a scale | Standard Deviation 6.98 |
| Galantamine + Placebo (Baseline) | The Quality of Life Assessment for Caregivers of Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | 36.50 scores on a scale | Standard Deviation 7.4 |
| Galantamine + Nimodipine (Week 8) | The Quality of Life Assessment for Caregivers of Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | 32.00 scores on a scale | Standard Deviation 9.03 |
| Galantamine + Placebo (Week 8) | The Quality of Life Assessment for Caregivers of Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | 33.56 scores on a scale | Standard Deviation 6.84 |
| Galantamine + Nimodipine (Week 24) | The Quality of Life Assessment for Caregivers of Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | 36.60 scores on a scale | Standard Deviation 4.56 |
| Galantamine + Placebo (Week 24) | The Quality of Life Assessment for Caregivers of Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | 34.88 scores on a scale | Standard Deviation 6.83 |
Primary
The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24
The Quality of Life assessment scale for patients with Alzheimer's disease (QoL-AD) is a 13-item scale with four possible scores for each question (score 1: poor and score 4: excellent). Total score ranges from 13 to 52. Higher scores represent a better outcome.
Time frame: Baseline, Week 8, Week 24
Population: Intent to Treat population, which consisted of all participants who used at least 1 study medication dose, had at least 1 evaluation after started use, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine + Nimodipine (Baseline) | The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | 33.56 scores on a scale | Standard Deviation 5.59 |
| Galantamine + Placebo (Baseline) | The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | 32.67 scores on a scale | Standard Deviation 7.02 |
| Galantamine + Nimodipine (Week 8) | The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | 35.60 scores on a scale | Standard Deviation 3.71 |
| Galantamine + Placebo (Week 8) | The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | 33.11 scores on a scale | Standard Deviation 4.68 |
| Galantamine + Nimodipine (Week 24) | The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | 36.60 scores on a scale | Standard Deviation 6.23 |
| Galantamine + Placebo (Week 24) | The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores at Baseline, Week 8, Week 24 | 33.86 scores on a scale | Standard Deviation 5.27 |
Primary
The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores, Based on the Caregiver's Opinion, at Baseline, Week 8, Week 24
The Quality of Life assessment scale for patients with Alzheimer's disease (QoL-AD), according to the opinion of the caregiver is a 13-item scale with four possible scores for each question (score 1: poor and score 4: excellent). It evaluates the opinion of the caregiver about the patient's quality of life. Total score ranges from 13 to 52. Higher scores represent a better outcome.
Time frame: Baseline, Week 8, Week 24
Population: Intent to Treat population, which consisted of all participants who used at least 1 study medication dose, had at least 1 evaluation after started use, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine + Nimodipine (Baseline) | The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores, Based on the Caregiver's Opinion, at Baseline, Week 8, Week 24 | 28.33 scores on a scale | Standard Deviation 8.62 |
| Galantamine + Placebo (Baseline) | The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores, Based on the Caregiver's Opinion, at Baseline, Week 8, Week 24 | 29.33 scores on a scale | Standard Deviation 8.08 |
| Galantamine + Nimodipine (Week 8) | The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores, Based on the Caregiver's Opinion, at Baseline, Week 8, Week 24 | 27.80 scores on a scale | Standard Deviation 5.36 |
| Galantamine + Placebo (Week 8) | The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores, Based on the Caregiver's Opinion, at Baseline, Week 8, Week 24 | 29.78 scores on a scale | Standard Deviation 6.69 |
| Galantamine + Nimodipine (Week 24) | The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores, Based on the Caregiver's Opinion, at Baseline, Week 8, Week 24 | 29.80 scores on a scale | Standard Deviation 5.76 |
| Galantamine + Placebo (Week 24) | The Quality of Life Assessment for Patients With Alzheimer's Disease (QoL- AD) Total Scores, Based on the Caregiver's Opinion, at Baseline, Week 8, Week 24 | 29.13 scores on a scale | Standard Deviation 7 |
Secondary
The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Baseline, Week 8, and Week 24
The ADAS-Cog is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation and praxis using an 11-point Assessment Scale. It has a minimum score of 0 and a maximum severity score of 70, and a higher score indicates more impairment.
Time frame: Baseline, Week 8, Week 24
Population: Intent to Treat population, which consisted of all participants who used at least 1 study medication dose, had at least 1 evaluation after started use, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine + Nimodipine (Baseline) | The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Baseline, Week 8, and Week 24 | 30.40 scores on a scale | Standard Deviation 13.81 |
| Galantamine + Placebo (Baseline) | The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Baseline, Week 8, and Week 24 | 28.20 scores on a scale | Standard Deviation 11.06 |
| Galantamine + Nimodipine (Week 8) | The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Baseline, Week 8, and Week 24 | 25.10 scores on a scale | Standard Deviation 9.21 |
| Galantamine + Placebo (Week 8) | The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Baseline, Week 8, and Week 24 | 31.03 scores on a scale | Standard Deviation 11.45 |
| Galantamine + Nimodipine (Week 24) | The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Baseline, Week 8, and Week 24 | 25.02 scores on a scale | Standard Deviation 9.75 |
| Galantamine + Placebo (Week 24) | The Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Baseline, Week 8, and Week 24 | 27.70 scores on a scale | Standard Deviation 12.16 |
Secondary
The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24
The Clinical Global Impression (CGI) is a scale to assess treatment response in patients with mental disorders. The Clinical Global Impression Improvement scale (CGI-I) requires the clinician to rate how much the patient's illness has improved or worsened relative to a baseline state. A patient's illness is compared to change over time and rated as: very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.
Time frame: Week 4, Week 8, Week 16, Week 24
Population: Intent to Treat population, which consisted of all participants who used at least 1 study medication dose, had at least 1 evaluation after started use, and with evaluable data at each measurement time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Galantamine + Nimodipine (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally worse | 1 participants |
| Galantamine + Nimodipine (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much improved | 1 participants |
| Galantamine + Nimodipine (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | No change | 4 participants |
| Galantamine + Nimodipine (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much worse | 0 participants |
| Galantamine + Nimodipine (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally improved | 1 participants |
| Galantamine + Nimodipine (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much improved | 0 participants |
| Galantamine + Nimodipine (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much worse | 0 participants |
| Galantamine + Placebo (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much improved | 0 participants |
| Galantamine + Placebo (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | No change | 4 participants |
| Galantamine + Placebo (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much worse | 0 participants |
| Galantamine + Placebo (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much improved | 1 participants |
| Galantamine + Placebo (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much worse | 0 participants |
| Galantamine + Placebo (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally worse | 0 participants |
| Galantamine + Placebo (Baseline) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally improved | 5 participants |
| Galantamine + Nimodipine (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally worse | 1 participants |
| Galantamine + Nimodipine (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally improved | 2 participants |
| Galantamine + Nimodipine (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much worse | 0 participants |
| Galantamine + Nimodipine (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much worse | 0 participants |
| Galantamine + Nimodipine (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much improved | 0 participants |
| Galantamine + Nimodipine (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | No change | 2 participants |
| Galantamine + Nimodipine (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much improved | 0 participants |
| Galantamine + Placebo (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | No change | 2 participants |
| Galantamine + Placebo (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much improved | 0 participants |
| Galantamine + Placebo (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much improved | 1 participants |
| Galantamine + Placebo (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally improved | 6 participants |
| Galantamine + Placebo (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally worse | 0 participants |
| Galantamine + Placebo (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much worse | 0 participants |
| Galantamine + Placebo (Week 8) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much worse | 0 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally improved | 2 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | No change | 1 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally worse | 1 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much improved | 1 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much worse | 0 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much improved | 0 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much worse | 0 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much improved | 0 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | No change | 5 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much worse | 0 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much improved | 0 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally improved | 3 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally worse | 0 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much worse | 0 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much improved | 0 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally improved | 3 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much worse | 0 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | No change | 1 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much worse | 0 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally worse | 0 participants |
| Galantamine + Nimodipine (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much improved | 1 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much worse | 0 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much worse | 0 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally worse | 1 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Very much improved | 0 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Minimally improved | 4 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | No change | 1 participants |
| Galantamine + Placebo (Week 24) | The Clinical Global Impression (CGI) at Week 4, Week 8, Week 16, and Week 24 | Much improved | 2 participants |
Secondary
The Neuropsychiatric Inventory (NPI) at Baseline, Week 8, and Week 24
The NPI evaluates 12 neuropsychiatric domains: delusions, hallucinations, dysphoria, anxiety, aggression, euphoria, dis-inhibition, irritability/lability, apathy, aberrant motor activity, eating disorders, and night-time behavior disturbances. For present domains, the severity and frequency of the behavior are determined. Frequency is rated 1 (rarely) to 4 (very often) and Severity is scored 1 (mild) to 3 (severe). The product scores vary from 1 (mild and rarely) to 12 (very often and severe). Total scores vary from 0 (no present domain) to 144 (all domains are present, are often and severe).
Time frame: Baseline, Week 8, Week 24
Population: Intent to Treat population, which consisted of all participants who used at least 1 study medication dose, had at least 1 evaluation after started use, and with evaluable data at each measurement time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine + Nimodipine (Baseline) | The Neuropsychiatric Inventory (NPI) at Baseline, Week 8, and Week 24 | 24.0 scores on a scale | Standard Deviation 14.72 |
| Galantamine + Placebo (Baseline) | The Neuropsychiatric Inventory (NPI) at Baseline, Week 8, and Week 24 | 26.92 scores on a scale | Standard Deviation 20.66 |
| Galantamine + Nimodipine (Week 8) | The Neuropsychiatric Inventory (NPI) at Baseline, Week 8, and Week 24 | 20.20 scores on a scale | Standard Deviation 8.67 |
| Galantamine + Placebo (Week 8) | The Neuropsychiatric Inventory (NPI) at Baseline, Week 8, and Week 24 | 22.11 scores on a scale | Standard Deviation 17.93 |
| Galantamine + Nimodipine (Week 24) | The Neuropsychiatric Inventory (NPI) at Baseline, Week 8, and Week 24 | 15.00 scores on a scale | Standard Deviation 11.55 |
| Galantamine + Placebo (Week 24) | The Neuropsychiatric Inventory (NPI) at Baseline, Week 8, and Week 24 | 19.75 scores on a scale | Standard Deviation 16.58 |